Original ArticlesLack of Association Between the Leptin Receptor Gene (LEPR) Gln223Arg Polymorphism and Late-onset Alzheimer DiseaseUtsunomiya, Kensuke MD, PhD* †; Shinkai, Takahiro MD, PhD*; Sakata, Shinichi MD*; Hwang, Rudi MSc‡; Yamada, Kenji MD*; Chen, Hsin-I MSc* §; Fukunaka, Yuko MD*; Ohmori, Osamu MD, PhD* ∥; Nakamura, Jun MD, PhD*Author Information *Department of Psychiatry, School of Medicine, University of Occupational and Environmental Health, Yahatanishi-ku ∥Wakato Hospital, Wakamatsu-ku, Kitakyushu †Health Management Department, Shimonoseki Shipyard and Machinery Works, Mitsubishi Heavy Industries, Ltd, Shimonoseki, Japan ‡Department of Psychiatry, Neurogenetics Section, Centre for Addiction and Mental Health, University of Toronto, Toronto, Ontario, Canada §Institute of Public Health, Kaohsiung Medical University, Kaohsiung, Taiwan This study was supported in part by the Grant-in-Aid numbers 18591319 and 20790863 for Scientific Research from the Ministry of Education, Science, Sports, and Culture, Japan (T.S. and S.S., respectively). Kensuke Utsunomiya is a 2007 award recipient of the Medical-Care-Education Research Foundation, Japan. Reprints: Kensuke Utsunomiya, MD, PhD, Department of Psychiatry, School of Medicine, University of Occupational and Environmental Health Yahatanishi-ku, Kitakyushu, 807-8555, Japan (e-mail: [email protected]) Received for publication November 14, 2008 accepted March 23, 2009 Alzheimer Disease & Associated Disorders: January 2010 - Volume 24 - Issue 1 - p 101-103 doi: 10.1097/WAD.0b013e3181b982dc Buy Metrics Abstract The principal hypothesis for pathogenesis of Alzheimer disease (AD) is the amyloid cascade hypothesis, which emphasizes an imbalance between production and clearance of β-amyloid (Aβ) in the brain. Insulin has important effects on the regulation of the Aβ level in the brain, modulating both Aβ production and clearance. An optimal brain insulin level promotes Aβ clearance, which may play protective roles against AD. A functional human leptin receptor gene (LEPR) polymorphism, a glutamine to an arginine substitution at codon 223 (Gln223Arg), has been associated with insulin resistance capacity and an altered leptin-binding activity. The LEPR Gln223Arg polymorphism may thus play an important role in the pathogenesis of AD. In this study, we examined the association between the LEPR Gln223Arg polymorphism and late-onset Alzheimer disease (LOAD) in a Japanese population. Our sample includes 49 patients with LOAD and 134 normal controls. Our preliminary data showed no significant association between the LEPR Gln223Arg polymorphism and LOAD (genotype distribution: χ2=0.11, df=2, P=0.945; allele frequency: χ2=0.058, df=1, P=0.81, odds ratio=1.08, 95% confidence interval=0.59 to 2.03). Our results suggest that the LEPR polymorphism may not play a major role in the development of LOAD. © 2010 Lippincott Williams & Wilkins, Inc.